PROJECT SUMMARY Patients with coexisting obesity and depression and common cardiometabolic risk factors are a critical target group for primary prevention because of their increasing prevalence and increased, but potentially reversible, lifetime risk for diabetes mellitus (DM) and cardiovascular disease. But little is known about how to treat them in concert in ways that are evidence-based and practical in primary care settings. The proposed study will test, for the first time, a clinical intervention that uniquely integrates the Group Lifestyle Balance (GLB) program for weight loss, which is a real-world translated model of the Diabetes Prevention Program lifestyle intervention, with the PEARLS collaborative stepped care program for depression, which uses problem-solving therapy (PST) as first-line with as-needed intensification through stepwise increases in doses and number of antidepressant medications. Obese, depressed adults with coexisting metabolic syndrome, pre- DM, and/or history of gestational DM will be the target patient population. Eligible and consenting primary care patients (n=404) from a large, community-based, multispecialty group practice will be randomized to receive the combined treatment or usual care for 12 months. Trained health coaches, working under co-located psychiatric and medical supervision, will provide 8 1-on-1 PST sessions over 5 months followed by 6 monthly calls. At the 4th 1-on-1 session, the coach will introduce the take-home GLB DVD, which has 12 weekly sessions and is supplemented by ongoing Web-, mobile- and email-mediated coach support for weight loss and behavior change. Following a stepped-care protocol, the supervising psychiatrist will recommend initiating or adjusting anti- depressant medications to primary providers of patients with unremitting symptoms, and if necessary, provide phone consultations to patients. Follow-up assessments will occur at 6, 12, 18, and 24 months. The primary aim is to determine the effectiveness of the intervention (E in the RE-AIM model). We hypothesize (1) that compared with controls, intervention participants will have better co-primary endpoints, i.e., lower mean BMI and score on the 20-item Depression Symptom Checklist at 12 months (end of treatment); (2) that these incremental intervention benefits will persist through 24 months (end of follow-up); and (3) that the intervention will show cost-effectiveness within 2 years and over a projected longer term, based on the ratio of incremental costs (estimated from health system and societal perspectives) to incremental benefits (expressed as quality-adjusted life years gained). The secondary aim is to conduct process evaluation with mixed methods for the other RE-AIM attributes: Reach (e.g., participation rate of the target population), Adoption (e.g., characteristics of participating clinics and providers), Implementation (e.g., fidelity of intervention delivery), and Maintenance (e.g., stakeholders' perceptions of intervention sustainability). We will also explore effect modifiers and mediators to enable intervention refinement for maximum impact. The proposed integrated multicondition approach to treating obesity and depression and cardiometabolic risk factors in primary care is novel and likely scalable, with high public health impact potential.